Neurologic dysfunction frequently accompanies HIV infection of children. The incidence of neurologic abnormalities is higher in HIV-1 infected children than in adults and the neurologic disease differs from that observed in adult AIDS patients. The reasons for these differences are obscure. A likely explanation is the immaturity of the host, specifically the developmental state of the CNS and immune system. Our hypothesis is that the clinical manifestations of HIV infection of the CNS in the immature host depend on: 1) the time of infection in relation to the developmental state of the CNS; 2) the virulence and tropism of the infecting virus; and 3) the immune status of the immature host at the time of infection. To evaluate this hypothesis we will use the SIV/macaque model of pediatric AIDS to address the following specific aims: 1) Determine the distribution and cellular targets of SIV in the CNS of fetal macaques inoculated in utero at different stages of development. 2) Determine the influence of viral determinants and neonatal immune status on the neuropathogenesis of SIV infection. This will initially involve infection of neonates with closely related molecular clones of SlV which differ in cell tropism and virulence. Subsequent experiments will examine the potential role of actively transferred maternal antibody in modifying the CNS infection. The ability to examine both host and viral determinants of disease over time makes the macaque model of pediatric AIDS extremely valuable for defining the pathogenesis of AIDS-related neurologic dysfunction.